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Biomedical subjects

S Navarro

Publications and source records attributed to S Navarro.

At least 109 records · Page 6Linked to original sources
PubMed1994

Role of zinc in the process of pancreatic fibrosis in chronic alcoholic pancreatitis.

Zinc acts as a cofactor in many enzymatic processes, including collagen synthesis. The observation of increased activity of prolylhydroxylase (PHase), an enzyme that takes part in the synthesis of collagen, in zinc-depleted liver tissue suggests that zinc deficiency is associated with hepatic collagen deposition. The pancreatic zinc content in chronic alcoholic pancreatitis (CAP) is still unknown. The objectives of this study were (a) To assess zinc concentrations in the pancreatic tissue in CAP; (b) to establish a possible relation between pancreatic zinc content, fibrosis, and PHase activity; and (c) to evaluate the relation between serum and pancreatic zinc levels. Sixteen surgical specimens of pancreatic tissue from patients with CAP were analyzed; control pancreatic samples from 11 organ donors were also studied. Zinc concentration, PHase activity, and the amount of fibrous tissue were assessed in the pancreatic tissue of each individual. The amount of fiber deposited in the pancreas in CAP was 68.4 +/- 19.8%, and that of the control group, 5 +/- 2% (p < 0.001). PHase activity in CAP was 754 +/- 230 cpm/mg of protein and that of the control group was 405 +/- 151 cpm/mg of protein (p < 0.001). The amount of pancreatic zinc in the former was 15.0 +/- 9.7 micrograms/g of tissue and that of the latter was 28.1 +/- 18.1 micrograms/g of tissue (p = 0.023). Serum zinc levels were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Acute necrotizing pancreatitis: a multicenter study.

A multicenter study of acute necrotizing pancreatitis (ANP) classified in accordance with the Balthazar criteria (grades D and E), has been performed in 12 teaching hospitals. A total of 233 patients were reviewed, and the mortality rate was 26.6%. The most common etiology was biliary pancreatitis (45.5%). Among the complications, shock, renal insufficiency, pulmonary insufficiency and hemorrhagic gastritis were associated with a mortality rate of 51-66%. Diffuse fluid collections were associated with a higher mortality rate (26.8%) than localized fluid collections (14.5%). In 106 patients with gallstone pancreatitis, early surgery was performed in 17, and 5 patients (29.4%) died. No mortality was observed in 32 patients with delayed surgery. Sphincterotomy was performed in 13 patients, and 4 (30.7%) died. Early surgery (necrosectomy and closed peritoneal lavage) was undertaken in 75 patients, with a mortality rate of 39%. In conclusion, the morbidity and mortality rates of ANP can be improved with proper monitoring, adequate supportive care and the judicious use of surgery based on clinical and morphological findings.

Acute Disease↗
PubMed1994

Comparison of Ewing's sarcoma of bone and peripheral neuroepithelioma. An immunocytochemical and ultrastructural analysis of two primitive neuroectodermal neoplasms.

Ewing's sarcoma of bone (ESB) and peripheral neuroepithelioma (PN) are frequently considered to be different tumors. Some researchers have suggested that PN is morphologically a neuroectodermal Ewing's sarcoma. We sought to determine the extent of neuroectodermal features in conventional ESB on direct patient material (25 cases) and to compare these tumors with a similar group of readily diagnosed PNs (10 cases). Light microscopic, ultrastructural, and immunophenotypic parameters were assessed and compared for both groups. The avidin-biotin complex method was used. All tumors were antigenically intact since all stained for vimentin or at least one marker. Neuroectodermal antigens (neuron-specific enolase, Leu-7 [HNK-1], neurofilament 200 kd, and S100) were found in nine of 10 cases of PN and in 17 of 25 cases of ESB. In ESB, an atypical light microscopic appearance correlated with the presence of neuroectodermal features in most cases, but neuroectodermal phenotype was more frequent (68%) than morphological evidence of neuroectodermal differentiation (36%). These data support the concept that ESB and PN are both peripheral primitive neuroectodermal neoplasms, differing only in extent of neuroectodermal phenotype and morphological differentiation.

Adolescent↗
PubMed1993

[Changes in the pancreatic and respiratory functions in cystic fibrosis. The influence of the time of the evolution of the disease].

BACKGROUND: Cystic fibrosis is the most frequent congenital disease in Caucasian and is transmitted by recessive autosomic inheritance. It is characterized by affection of different glands of exocrine secretion, particularly the pancreas and the lung. The aim of this study was to analyze the degree of alteration of pulmonary and pancreatic exocrine function in a group of patients with cystic fibrosis in relation to the time of disease evolution. METHODS: Twenty-one patients between 9 and 31 years of age were studied; 11 with an evolution of lower than or equal to 158 months and 10 with an evolution of higher than 158 months (median of the total patients). To study pancreatic exocrine function the BT-PABA test immunoreactive serum trypsin test were used. To evaluate respiratory function FEV1, FVC, FEV1/FVC ratio and PaO2 were used. RESULTS: The results obtained demonstrated that in the group with a lower time of evolution the diagnosis had been carried out at earlier ages (17 +/- 17 months versus 84 +/- 60 months; p = 0.002) and presented a significantly more altered pancreatic exocrine function (BT-PABA: 13 +/- 12% versus 35 +/- 23%; p = 0.013). However, respiratory function was altered in the group with longer time of evolution (FEV1: 68 +/- 20% versus 36 +/- 23%; p = 0.003; FVC: 74 +/- 9 versus 52 +/- 25%; p = 0.013; FEV1/FEV: 77 +/- 19 versus 50 +/- 9%; p < 0.001; PaO2: 84 +/- 16 versus 58 +/- 11%; p < 0.001). CONCLUSIONS: Pancreatic exocrine function is most intensely affected in patients diagnosed with cystic fibrosis at earlier and with shorter times of evolution while patients who have the longest time of evolution and who were diagnosed later in life presented greater changes in respiratory function.

Adolescent↗
PubMed1993

An improved Bradford protein assay for collagen proteins.

A modification of the protein determination method of Bradford adapted for collagen-rich samples is described. The use of Coomassie-based protein determination methods is limited by the great variation in colour yield obtained for different proteins. This is especially important in samples containing significant amounts of collagen where direct application of the methods of Lowry and Bradford results in underestimated values. Addition of small amounts of sodium dodecyl sulphate (SDS) (0.0035%) to the diluted solutions of Coomassie Brilliant Blue G used as dye reagent in the Bradford colorimetric assay caused a 4-fold increase in the colour response of three collagen proteins (Col I, III and IV) and a decrease in absorbance for various non-collagen proteins. The presence of SDS in the reagent did not result in a significant metachromatic shift of the collagen-dye complexes. This simple modification in the preparation of the reagent for the Bradford assay allows similar response curves to be obtained for collagen and non-collagen proteins, making the modified assay of potential use for protein determination in collagen-rich samples such as pancreatic extracts.

Collagen↗
PubMed1993

Ursodeoxycholic acid treatment of primary hepatolithiasis in Caroli's syndrome.

Congenital cystic dilation of the intrahepatic bile ducts (Caroli's syndrome) is a rare cause of chronic cholestasis and hepatolithiasis in young adults. Long-term prognosis is poor even with surgical drainage. We treated twelve patients who had Caroli's syndrome and intrahepatic stones with ursodeoxycholic acid (UDCA), 10-20 mg/kg daily. The duodenal bile of these patients contained cholesterol crystals, which suggests that the stones were cholesterol rich. UDCA led to sustained clinical remission, return to normal liver function, and dissolution of intrahepatic stones on ultrasound in all patients (nine partial, three complete) after 48 (range 12-114) months' follow-up. Litholytic therapy is indicated for intrahepatic stones in Caroli's syndrome.

Adult↗
PubMed1993

[Isolated rectal Kaposi's sarcoma].

We report a case of isolated rectal Kaposi's Sarcoma in a homosexual man with active Human Immunodeficiency Virus infection. Although gastrointestinal tract affection is not infrequent, it is usually associated with the existence of skin lesions. A few cases of noncutaneous gastrointestinal Kaposi's Sarcoma have been described, but no one affecting only the rectum. This is a diagnostic possibility in patients with Human Immunodeficiency Virus infection and rectal symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1993

dbl oncogene expression in childhood tumors and tumor cell lines.

We studied the expression of the dbl oncogene in the total RNA obtained from a wide spectrum of childhood tumors, including Ewing's sarcomas, peripheral neuroectodermal tumors (PNET), esthesioneuroblastomas, neuroblastomas, retinoblastomas, rhabdomyosarcomas, osteosarcomas, and synovial sarcomas. Material was obtained from primary tumors, nude mice xenografts, and tumor cell lines. Following the Northern blot technique, a single band of 2.8 kb was found in each analyzed case. Induction of neural differentiation in Ewing's sarcoma, peripheral PNET, and neuroblastoma cell lines with dibutyryl cyclic AMP did not change the expression of the dbl oncogene. We conclude that the wide expression of the dbl oncogene in these childhood tumors reduces its value as a molecular marker for their differential diagnosis; on the other hand, the dbl oncogene does not appear to be an essential molecular factor in the process of neuroectodermal differentiation of small round cell tumors of childhood.

Animals↗
PubMed1992

Multicenter double-blind trial of gabexate mesylate (FOY) in unselected patients with acute pancreatitis.

A multicenter, randomized, double-blind trial was carried out to evaluate the efficacy of gabexate mesylate (FOY) in acute pancreatitis. One hundred unselected patients were randomly allocated into two groups: 51 were assigned to receive FOY (12 mg/kg/day as continuous intravenous infusion for a minimum of 4 days and a maximum of 12 days), and 49 were allocated to placebo. The groups were comparable in demographic, clinical and biochemical parameters, etiology of pancreatitis, and disease severity, which was generally mild. Gallstones were the main etiological factor. All patients received fluid and electrolyte replacement, analgesia and nasogastric suction for at least 48 h after admission. Experimental therapy was initiated no later than 12 h after the beginning of symptoms. The results showed no statistically significant differences between the two groups with respect to the evolution of clinical and biochemical parameters, analgesic requirements, development of complications, hospitalization time or mortality at completion of the trial. In conclusion, early treatment with FOY does not appear to have any demonstrable beneficial effects in acute pancreatitis.

Acute Disease↗
PubMed1992

Dynamic model of differentiation in Ewing's sarcoma cells. Comparative analysis of morphologic, immunocytochemical, and oncogene expression parameters.

We report the establishment of a model of neural differentiation in four well-characterized Ewing's sarcoma cell lines. This process was induced by serum-depleted medium (1% fetal bovine serum) and agents such as dibutyryl cyclic AMP and retinoic acid. The morphologic changes were characterized predominantly by the presence of neurite-like elongated processes showing varicosities and branching along their course with numerous internal filaments and electron-dense granules. Immunocytochemically, differentiation was accompanied by a considerable increase in reactivity for neural markers of several types: neuroblastic, neuroepithelial, neuroendocrine, Schwannian and even glial. In contrast, the tumor promoter, phorbol 12-myristate 13-acetate inhibited differentiation. Several morphologic changes were observed in phorbol 12-myristate 13-acetate-treated cells: the cells became smaller and rounder, were poorly adherent to substrate, by electron microscopy lacked cytoplasmic organelles, electron-dense granules or neural processes, and showed decreased expression of neural markers. Northern blot analysis was performed to establish whether there was any relationship between neural differentiation and degree of N-myc, c-myc and dbl oncogene expression. There was no N-myc oncogene expression in the mRNA of Ewing's sarcoma cells, even after neural induced differentiation. The degree of c-myc and dbl oncogene expression appeared heterogeneous, and varied with the culture condition. Based on these results, it may be inferred that Ewing's sarcoma cells in vitro display a variable neural phenotype, there being a variety of biologic responses to diverse culture media and various differentiation agents, but with no consistent effect on N-myc, c-myc and dbl oncogene expression.

Bucladesine↗
PubMed1992

c-jun and c-fos are expressed by human megakaryocytes.

Expression of the main nuclear protooncogenes during terminal megakaryocyte (MK) differentiation is poorly understood. Because previous results have suggested that c-fos and c-jun protooncogenes are expressed in human leukemic cell lines induced to undergo megakaryocytic differentiation, we have analyzed the expression of these two protooncogenes in normal MK. Studies were performed, by in situ hybridization and immunofluorescence, on human MK obtained either directly from bone marrow or from culture of MK progenitors. c-fos and c-jun transcripts were detected in most cultured or fresh marrow MK from adult donors. Expression was much higher in cytologically immature than in mature MK whereas no expression was detected in the most mature MK. c-fos and c-jun expression increased dramatically with MK size. In cultured fetal MK, which all remained small in size, c-fos mRNA was present but at a low level. The c-fos-encoded protein (P62fos) was easily detectable in the great majority of MK. We directly demonstrated that the level of P62fos expression was correlated to MK ploidy by flow cytometry using a three-color staining technique. The involvement of serum and growth factors in the induction of P62fos in MK was studied. Whereas a 3-h serum deprivation resulted in the disappearance of P62fos in MK, several growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), interleukin 6 (IL-6), interleukin 7 (IL-7), leukemia inhibitory factor (LIF), and transforming growth factor beta (TGF-beta), as well as normal or aplastic serum, were able to reinduce its expression within 2 h. In conclusion, our results suggest that c-jun and c-fos may play a role in the transduction of signals by several growth factors during terminal MK differentiation.

DNA-Binding Proteins↗
PubMed1991

Characterization of murine hematopoietic progenitor subsets involved in interleukin-3-induced interleukin-6 production.

Various murine cell populations were tested for their ability to generate interleukin-6 (IL-6) in response to IL-3. Among these, bone marrow cells exhibit the most prominent IL-6 production. The responder cells in this organ have been further characterized by cell fractionation on a discontinuous Ficoll gradient, fluorescence-activated cell sorting, and in situ hybridization. These procedures have allowed us to ascribe the following features to the cells mainly responsible for IL-3-induced IL-6 production: (1) they possess a low density and a relatively high forward and perpendicular light scatter (FLS/PLS); (2) they are characterized by a high rhodamine (Rh) retention; and (3) their enrichment in various subpopulations is similar to that obtained for progenitors forming colonies in the methylcellulose assay colony-forming units (CFU-C). In contrast, IL-3 target cells in terms of IL-6 production are absent both in the mature and in the most immature bone marrow compartment. Indeed, the Rh-dull population that is enriched for cells with marrow repopulating activity does not respond to the growth factor and mature cells cannot be induced to express IL-6 as assessed by (1) FLS/PLS characteristics, (2) the monoclonal antibody ER-MP 20 recognizing monocytes and granulocytic cells, and (3) in situ hybridization. Taken together, our data support the conclusion that the bone marrow cells generating IL-6 in response to IL-3 belong to a progenitor population with enhanced mitochondrial activity, comprising probably several types of immature cells of the myeloid lineage including macrophage/granulocyte precursors.

Animals↗
PubMed1991

In vitro effects of hematopoietic growth factors on the proliferation, endoreplication, and maturation of human megakaryocytes.

A liquid culture technique was used to study regulation of human megakaryocytopoiesis in vitro. Low-density cells from adult bone marrow were cultured in the presence of normal plasma, plasma from patients with aplastic marrows (AP), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and interleukin-3 (IL-3). Megakaryocytes (MK) were studied at day 10 of culture by a two-color staining technique using a pool of monoclonal antibodies for their identification and propidium iodide to label DNA. Their ploidy distribution was analyzed by flow cytometry. In some experiments cytoplasmic maturation was also studied by ultrastructural techniques. Normal plasma provides a low number of MK with a ploidy distribution including 8 N and 16 N MK. AP promoted in a dose-dependent manner proliferation of MK and some batches favored endoreplication. This effect was clearly demonstrated when ploidy distribution was compared between normal plasma and AP on parallel marrow cultures. However, ploidy distribution was shifted toward low values compared with uncultured MK. rhGM-CSF had no significant effect on these two parameters. In contrast, rhIL-3 from 0.1 U/mL to 100 U/mL had a proliferative effect but was unable to induce endoreplication. Furthermore, when associated with AP it totally abrogated the effect of AP on endoreplication because in most experiments more than 90% of MK were 2 N and 4 N. This effect was also observed when rhIL-3 was added after 7 days of culture (when it has little proliferative effects). Studies of the maturation of MK grown with rhIL-3 indicate that the majority were small mature cells synthesizing alpha-granules and demarcation membranes. The effect of AP on MK proliferation and endoreplication was not related to IL-6 because its IL-6 content was identical to that of normal plasma and its neutralization did not modify these parameters. In conclusion, this study indicates that liquid culture technique in association with flow cytometry could be a powerful tool in identifying the humoral regulators of human megakaryocytopoiesis.

Anemia, Aplastic↗
PubMed1991

Interleukin-6 and its receptor are expressed by human megakaryocytes: in vitro effects on proliferation and endoreplication.

Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in the megakaryocytic differentiation. Recently, we have observed that IL-6 is synthesized by several human cell lines with megakaryocytic features. In this study, we have investigated whether a similar phenomenon occurs during normal megakaryocytic differentiation. Human megakaryocytes (MK) were obtained by culturing normal marrow in liquid culture with aplastic plasma (AP). First, an IL-6 secretion in bone marrow culture enriched in MK as well as in purified MK populations was demonstrated by a biologic assay. Second, IL-6 mRNA was detected in a purified population of MK by the polymerase chain reaction and dot blot analysis. IL-6 mRNA and protein were undetectable in platelets. Third, in situ hybridization procedure demonstrated the presence of IL-6 mRNA in individual immature MK. Fourth, IL-6 protein was detected in MK at the unicellular level by an immunoalkaline phosphatase technique using a monoclonal antibody against IL-6. Furthermore, the presence of IL-6 receptor (IL-6-R) on MK was demonstrated by in situ hybridization using an IL-6-R probe and in situ autoradiography after binding with [125I]-labeled recombinant IL-6. The IL-6 endogenously produced in liquid cultures containing normal human plasma or AP was subsequently neutralized. This resulted in a 50% decrease of the MK growth with a minor shift in the ploidy distribution toward lower values. In semisolid cultures the addition of anti-IL-6 antibodies led to a 42% decrease in colony number in cultures stimulated by IL-3 but not in other conditions of culture. These results suggest that normal human megakaryocytopoiesis might be regulated in part by an IL-6 autocrine loop.

Antibodies, Monoclonal↗
PubMed1991

Quantitative measurement of fibrosis in pancreatic tissue. Evaluation of a colorimetric method.

A colorimetric method has been used to quantify the collagen contained in 23 specimens of pancreatic tissue (11 controls and 12 chronic pancreatitis). The method takes advantage of the selective capacity of Sirius red to stain collagen protein and of rapid green to stain noncollagen protein. The results obtained by this method were compared with those of standard morphometry to determine tissue fibrosis. With the morphometric method, the values of the control group were 6.6 +/- 4.0% (fiber area/total area), and those of chronic pancreatitis 66.0 +/- 19.0% (difference 59.4, 95% confidence interval for difference: 47.2-71.6, P less than 0.001). The values obtained with the colorimetric method were 89.1 +/- 11.6 micrograms collagen/mg total protein in the control group, and 132.7 +/- 25.3 micrograms collagen/mg total protein in the chronic pancreatitis group (difference 43.6, 95% confidence interval for difference: 26.3-61.0, P less than 0.001). A highly significant correlation (r = 0.847; p less than 0.001) was observed between the amount of collagen measured colorimetrically and the degree of fibrosis determined morphometrically. These results demonstrate that the colorimetric method is a reproducible, simple, and rapid technique to quantitate fibrosis in histological preparations of pancreatic tissue.

Alcoholism↗
PubMed1991

Occult microlithiasis in 'idiopathic' acute pancreatitis: prevention of relapses by cholecystectomy or ursodeoxycholic acid therapy.

Gallstone pancreatitis is usually related to small stones, which may not be detected by conventional cholecystographic techniques. In the current study, it was hypothesized that some patients with acute pancreatitis of unknown cause could harbor occult microstones in the gallbladder. Therefore, evidence was sought prospectively of missed gallstones by biliary drainage and microscopic examination of centrifuged duodenal bile in 51 patients recovering from an attack of acute pancreatitis, including 24 patients with relapsing episodes. Clusters of cholesterol monohydrate crystals, calcium bilirubinate granules, and/or CaCO3 microspheroliths were found in 67% of the patients. Biliary drainage showed no abnormal findings in 12 patients convalescing from a bout of known alcoholic pancreatitis. Examination of gallbladder bile at cholecystectomy and/or serial ultrasonography of the gallbladder for up to 12 months showed that 73% of the patients with unexplained pancreatitis had biliary sludge or microlithiasis; the prior finding of biliary crystal/solid markers predicted their existence with both a sensitivity and a specificity of 86% and a predictive value of 94%. The probability of harboring occult gallstones was also associated with age (P = 0.004), prior recurrent pancreatitis (P = 0.024), and altered liver function tests results during an index episode (P = 0.003). In 13 patients with cholesterol monohydrate crystals in bile, ursodeoxycholic acid (10 mg.kg-1.day-1) eliminated gallbladder microlithiasis within 3-6 months, and subsequent maintenance treatment with a daily dose of 300 mg prevented both gallstone recurrence and further attacks of pancreatitis over a mean follow-up period of 44 months. Cholecystectomy also prevented gallstone-associated relapses in 17 of 18 patients followed up for a mean postoperative period of 36 months. This study provides firm evidence showing that in most patients with idiopathic acute pancreatitis, the disease is related to microscopic gallstones, as evidenced by the follow-up development of macroscopic stones or sludge and by the prevention of relapses with either cholecystectomy or a cholelitholytic bile acid. Occult gallstones should be strongly suspected when acute pancreatitis of unknown cause occurs in a relapsing manner and in aged patients and when it is associated with altered liver function test results. Biliary microscopy and/or follow-up ultrasonography of the gallbladder provide a simple means of uncovering them to institute appropriate therapy and prevent further attacks.

Acute Disease↗
PubMed1991

Chronic diarrhea with normal stool and colonic examinations: organic or functional?

To investigate whether the clinical history and basic laboratory test results can differentiate between an organic or functional cause of chronic diarrhea and thus avoid unnecessary hospital admissions and invasive procedures, we reviewed the charts of 58 adult patients admitted during 6 years because of chronic diarrhea who had normal stool and colonic examinations. The final diagnoses were irritable bowel syndrome in 34 patients, organic diarrhea in 21, and unknown cause in three. The following clinical data did not help in the differential diagnosis: age, sex, duration of diarrhea, presence of continuous diarrhea, abdominal pain, stool frequency or volume, and presence of stool mucus. Significant weight loss, nocturnal diarrhea, and the absence of tenesmus were associated with an organic cause. One or more laboratory alterations (increased erythrocyte sedimentation rate, anemia, hypokalemia, and low serum albumin level) were found in 62% of patients with organic diarrhea but in only 3% of those with functional disease; p less than 0.001. In 20 of 21 patients with organic diarrhea, an syndromic diagnosis (fat malabsorption, n = 13; inflammatory bowel disease, n = 4; and secretory diarrhea, n = 3) could be obtained with three simple tests (stool fat, rectal biopsy, and fecal water osmolality and electrolyte determination, respectively). Our study confirms that a detailed history and a few simple laboratory data can help to distinguish between functional and organic diarrhea and so avoid extensive investigation. The syndromic diagnosis of organic diarrhea can also be approximated with relatively easy tests.

Barium Sulfate↗